With the widespread use of antiretroviral therapy, non-AIDS-related conditions such as cardiovascular disease and chronic kidney disease have emerged as important risk factors for mortality in the aging HIV-infected population. In the United States, cardiovascular disease is now the 3rd leading cause of death among HIV- infected persons and the prevalence of end-stage renal disease due to HIV has doubled over the past decade. Among HIV-infected individuals, cardiovascular disease may be associated with traditional risk factors, HIV- related factors, and antiretroviral medications. While kidney disease is an established risk factor for cardiovascular events including myocardial infarction, stroke, heart failure, and peripheral arterial disease in the general population, no studies have been conducted in HIV-infected persons. In addition, antiretroviral therapy has been associated with adverse effects on both the kidney and heart;specifically, abacavir and tenofovir have been implicated in cardiovascular and renal adverse events, respectively. The central purpose of this research proposal will be to advance our understanding of cardiovascular disease in HIV infection by defining the relationship between kidney disease, antiretroviral therapy, and cardiovascular events using a national registry of HIV-infected US veterans. We have 3 specific aims: (1) to describe the association between kidney disease and cardiovascular events in HIV-infected persons;(2) to critically reevaluate the association of abacavir with CVD by accounting for CKD and utilizing advanced statistical methods;and (3) to describe tenofovir-associated changes in kidney function and their association with cardiovascular disease. This study will provide the foundation for translational research that define pathogenic mechanisms for the association between kidney disease and cardiovascular events, and prospective clinical studies of interventions and process measures to enforce safe use of abacavir and tenofovir. PUBLIC HEALTH RELEVANCE: Kidney disease and cardiovascular events are major complications of antiretroviral therapy in HIV-infected persons. The proposed research will help elucidate the roles of kidney disease and antiretroviral therapy in determining cardiovascular risk and help guide safer use of these medications.